title: A signature inferred from Drosophila mitotic genes predicts survival of breast cancer patients.
abstract: BACKGROUND
  The classification of breast cancer patients into risk groups provides a powerful tool for the identification of patients who will benefit from aggressive systemic therapy. The analysis of microarray data has generated several gene expression signatures that improve diagnosis and allow risk assessment. There is also evidence that cell proliferation-related genes have a high predictive power within these signatures.
  
  
  METHODS
  We thus constructed a gene expression signature (the DM signature) using the human orthologues of 108 Drosophila melanogaster genes required for either the maintenance of chromosome integrity (36 genes) or mitotic division (72 genes).
  
  
  RESULTS
  The DM signature has minimal overlap with the extant signatures and is highly predictive of survival in 5 large breast cancer datasets. In addition, we show that the DM signature outperforms many widely used breast cancer signatures in predictive power, and performs comparably to other proliferation-based signatures. For most genes of the DM signature, an increased expression is negatively correlated with patient survival. The genes that provide the highest contribution to the predictive power of the DM signature are those involved in cytokinesis.
  
  
  CONCLUSIONS
  This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible target for antimitotic therapies.
authors.affiliation: Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Damasco
authors.forename: Antonio
authors.initials: A
authors.lastname: Lembo
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Somma
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gatti
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D019295:Computational Biology; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D017344:Genes, Insect; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D017385:Sequence Homology; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor